A review of the data quality and comparability of case-control studies of low-level exposure to benzene in the petroleum industry

Three nested case-control studies (in Canada, UK and Australia) of risks of leukaemia following low exposures to benzene in the distribution of petroleum (gasoline) produced apparently inconsistent results: the Canadian study reported no excess risks at the exposure levels studied, the Australian study reported risks especially at higher exposures, and the UK study gave indeterminate results.Through site visits, structured discussions with the investigators, and detailed reading of published and unpublished study reports, we reviewed and audited the methods used for selecting cases and controls, for estimating individual exposures, and for analysing and interpreting the data. Where possible, we examined the data graphically.We found that: all of the studies had been well performed; there were no issues of subject selection, methods or general data quality that were likely to have distorted their internal comparisons; we could not check whether the metric for exposure assessments is the same across the studies; the exposure assessments for the Australian study required the least backward estimation, and the Canadian, which also had fewest cases, the most; evidence of an increased risk at higher exposures in Australia was convincing.Given the relative strengths of the three studies, the findings are consistent with some effect of benzene at the high end of the subjects’ lifetime exposures. An analysis pooling data from all three studies would improve quantification of any exposure-response relationship, but would benefit from preliminary work to demonstrate or improve comparability of the exposure assessments and of cell typing in the cases. “”